The first part of this program covers the study of the primary structure collagen as it relates to binding and cleavage by animal collagenases and the binding of LETS glycoprotein, the mode of intracellular packaging of procollagen by e.m., the relationship of this process to fibrogenesis, and the influence of matrix material, such as proteoglycans and haluronic acid in regulating developmental processes. The second part covers the mechanics of connective tissue degradation in inflammatory joint disease with emphasis on the production of collagenase and prosoglandin, the isolation and identification of the controls of production of these substances, the effects of hormones, calcitonin, and prostaglandin E) on cell cultures from human connective tissues in order to assess factors that control collagen synthesis in human, particularly with respect to heritable disorders of connective tissue, and to develop a specific assay for guinea pig antigenic factor. The last part covers the study of the biosynthesis of glycoproteins and proteoglycans by use of chemically synthesized isoprenoid sugar phosphates as intermediates and endogenous or synthetic peptides and glycopeptides as acceptors; and the isolation and structure identification of urinary glycopeptides and oligosaccharides from patients with connective tissue diseases.